Inhibitors of the interaction between HMGB polypeptides and toll-like receptor 2 as anti-inflammatory agents
View Patent ↗The invention features a method of treating an inflammatory condition in an individual, comprising administering an agent inhibits the interaction between a Toll-like receptor 2 (TLR2) and a high mobility group B (HMGB) polypeptide to the individual. The invention also features methods for identifying agents that inhibit the interaction between TLR2 and HMGB.
1. A method of treating an inflammatory condition in an individual in need thereof, comprising administering to said individual an effective amount of an agent that inhibits the interaction between a high mobility group B (HMGB) polypeptide or functional equivalent thereof and Toll-like receptor 2, wherein the agent is soluble Toll-like receptor 2 and wherein the inflammatory condition is peritonitis, pancreatitis, ulcerative colitis, Crohn's disease, organ ischemia, reperfusion ischemia, cachexia, burns, myocardial ischemia, adult respiratory distress syndrome, multiple sclerosis, restenosis, rheumatoid arthritis, systemic lupus erythematosus, Behcet's syndrome, psoriasis, allograft rejection or graft-versus-host disease.
2. The method of claim 1 , wherein said agent binds said Toll-like receptor 2 and inhibits binding by a high mobility group B (HMGB) polypeptide or functional equivalent thereof.
3. The method of claim 1 , wherein said HMGB polypeptide is mammalian.
4. The method of claim 3 , wherein said HMGB polypeptide is HMGB1.
5. The method of claim 1 , wherein the disorder is rheumatoid arthritis, systemic lupus erythematosus, or allograft rejection.
6. An in vitro method of determining whether an agent inhibits inflammation, comprising:
(a) contacting a Toll-like receptor 2 with said agent and an HMGB polypeptide or a functional equivalent thereof; and
(b) detecting binding of an HMGB polypeptide to said Toll-like receptor 2, wherein an agent that decreases binding of said HMGB polypeptide to said Toll-like receptor 2 relative to a suitable control is an agent that inhibits inflammation.
7. The method of claim 6 , wherein said HMGB polypeptide or functional equivalent thereof is mammalian.
8. The method of claim 7 , wherein said HMGB polypeptide is HMGB1.
9. The method of claim 6 , wherein said Toll-like receptor 2 is on the surface of a cell.
10. The method of claim 9 , wherein said cell is a macrophage.
11. The method of claim 10 , wherein the macrophage is a human macrophage.